1ETH

TRIACYLGLYCEROL LIPASE/COLIPASE COMPLEX

Summary for 1ETH

• Entry DOI: 10.2210/pdb1eth/pdb
• Descriptor: TRIACYLGLYCEROL ACYL-HYDROLASE, COLIPASE, beta-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: complex (hydrolase-cofactor), lipid degradation, complex (hydrolase-cofactor) complex, complex (hydrolase/cofactor)
• Biological source: Sus scrofa (pig); More
• Cellular location: Secreted: P00591 P02703
• Total number of polymer chains: 4
• Total formula weight: 123740.85

Authors

Hermoso, J.,Pignol, D.,Kerfelec, B.,Crenon, I.,Chapus, C.,Fontecilla-Camps, J.C. (deposition date: 1995-09-13, release date: 1996-12-07, Last modification date: 2020-07-29)

Primary citation

Hermoso, J.,Pignol, D.,Kerfelec, B.,Crenon, I.,Chapus, C.,Fontecilla-Camps, J.C.
Lipase activation by nonionic detergents. The crystal structure of the porcine lipase-colipase-tetraethylene glycol monooctyl ether complex.
J.Biol.Chem., 271:18007-18016, 1996

PubMed Abstract: The crystal structure of the ternary porcine lipase-colipase-tetra ethylene glycol monooctyl ether (TGME) complex has been determined at 2.8 A resolution. The crystals belong to the cubic space group F23 with a = 289.1 A and display a strong pseudo-symmetry corresponding to a P23 lattice. Unexpectedly, the crystalline two-domain lipase is found in its open configuration. This indicates that in the presence of colipase, pure micelles of the nonionic detergent TGME are able to activate the enzyme; a process that includes the movement of an N-terminal domain loop (the flap). The effects of TGME and colipase have been confirmed by chemical modification of the active site serine residue using diisopropyl p-nitrophenylphosphate (E600). In addition, the presence of a TGME molecule tightly bound to the active site pocket shows that TGME acts as a substrate analog, thus possibly explaining the inhibitory effect of this nonionic detergent on emulsified substrate hydrolysis at submicellar concentrations. A comparison of the lipase-colipase interactions between our porcine complex and the human-porcine complex (van Tilbeurgh, H., Egloff, M.-P., Martinez, C., Rugani, N., Verger, R., and Cambillau, C.(1993) Nature 362, 814-820) indicates that except for one salt bridge interaction, they are conserved. Analysis of the superimposed complexes shows a 5.4 degrees rotation on the relative position of the N-terminal domains excepting the flap that moves in a concerted fashion with the C-terminal domain. This flexibility may be important for the binding of the complex to the water-lipid interface.

PubMed: 8663362
DOI: 10.1074/jbc.271.30.18007

Experimental method

X-RAY DIFFRACTION (2.8 Å)